Effect of Fingolimod on Neurodegeneration

NCT02575365 | Terminated Phase 4 Results

• 1 other identifier: CFTY720DTR05
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 3

Brief Summary

This was a 24-month, open-label, multicenter study with a single treatment arm design. Primary objective of this study was:

• To investigate the effects of Fingolimod on cognitive performance in highly active relapsing remitting multiple sclerosis patients Secondary objectives of this study were:
• To investigate the correlation between the effect of fingolimod on cognitive performances and MRI data.
• To evaluate the effect of fingolimod on biomarkers (24 hydroxy cholesterol, osteopontin and matrix metalloproteinases) related to neurodegeneration
• To investigate the effect of fingolimod on brain gray matter atrophy and thalamic atrophy. Polulation The hope was to recruit a minimum of 80 relapsing remitting MS (RRMS) patients according to the McDonald criteria.

Conditions

Cognition; Brain Volume Loss

Keywords

RRMS,; Cognition,; brain,; Fingolimod,; Multiple Sclerosis,; neurodegeneration,; Brain atrophy,; gray matter atrophy,; thalamic atrophy,; biomarkers,; BICAMS Battery,

Outcome Measures

Primary Outcomes (2)

• Change From Baseline in The Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) Battery Test at 12 Months

  The Brief International Cognitive Assessment for MS ( BICAMS Battery ) includes 3 cognitive tests, 1-Symbol Digit Modalities Test (SDMT, 2-the second edition of the California Verbal Learning Test (CVLT2) and 3-the revised Brief Visuospatial Memory Test (BVMTR).

  baseline , month 12.

• Change From Baseline in The Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) Battery Test at 24 Months

  The Brief International Cognitive Assessment for MS (BICAMS Battery) includes 3 cognitive tests, 1-Symbol Digit Modalities Test (SDMT, 2-the second edition of the California Verbal Learning Test (CVLT2) and 3-the revised Brief Visuospatial Memory Test (BVMTR).

  baseline and month 24

Secondary Outcomes (5)

• Change From Baseline in PASAT Test

  baseline ,months 6, month 12 and month 24

• Change From Baseline in Stroop Test

  baseline, month 6, month 12 and month 24

• Change From Baseline in Brain Gray Matter Atrophy and Thalamic Atrophy

  baseline, month 6, month 12, month 18 and month 24

• Change From Baseline in Serum Levels of 24S-hydroxycholesterol (24OHC) , Osteopontin and Matrix Metalloproteinases (and Also MMPI's)

  baseline, month 6, month , month 12 and month 24

• the Correlation Between Effect of Fingolimod on Cognitive Performances and Brain Atrophy (Gray Matter Atrophy and Thalamic Atrophy) by Comparing Baseline and Month 24.

  baseline, month 24

Study Arms (1)

Fingolimod arm

EXPERIMENTAL

0.5 mg p.o fingolimod daily

Drug: 0,5 mg Fingolimod

Interventions

0,5 mg Fingolimod DRUG

0.5 mg p.o fingolimod daily

Fingolimod arm

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosed with RRMS as described in 2010 McDonald criteria (36)
• Provided written informed consent prior to any intervention
• Unresponsive to treatment with a beta interferon or glatiramer acetate for a minimum of one year at and at adequate dose and with high disease activity .
• (Unresponsive patients: patients with no changes in relapses, increased relapses, severer relapses with one-year treatment or those who had had at least one relapse during the past one year under previous treatments and one or multiple contrast enhancing lesions in cranial MRI or increased T2 lesions in successive MRIs)
• EDSS score below 5.5 at screening

You may not qualify if:

• \. Patients with primary or secondary progressive or progressive relapsing MS. 2. Patients with known contraindications for fingolimod treatment. 3. Other coexistent autoimmune diseases including Hashimoto thyroiditis, systemic lupus erythematosus, rheumatoid anthiritis, psoriasis etc.
• \. Patients with any of the following cardiovascular conditions:
• Resting heart rate \< 45 bpm/min
• Cardiac failure at any time during the first study visit (Class III as per NYHA classification) or significant heart disease as judged by the physician
• Myocardial infarction during the last 6 months
• History of Mobitz Type II grade 2 AV block
• Past or current grade 3 AV block
• Confirmed history of sick sinus syndrome or sino-atrial heart block
• arrhythmia requiring current treatment with Class Ia drugs (ajmaline, disopyramid, procainamide, quinidine)
• hypertension uncontrolled with medication 5. History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.
• \. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, detected by urinalysis and confirmed by a positive hCG laboratory test.
• \. Negative for varicella-zoster virus IgG antibodies at screening. Patients who have negative results for varicella-zoster virus IgG antibodies can be included in the study after vaccination for varicella-zoster virus.
• \. Active systemic bacterial, viral or fungal infections, or diagnosis of AIDS, Hepatitis B, Hepatitis C infection defined as a positive HIV antibody, Hepatitis B surface antigen or Hepatitis C antibody tests, respectively 9. History of previous fingolimod therapy 10. Patient who received any of the treatments below:
• Corticosteroids or adrenocorticotropic hormone (ACTH) during the last 1 month
• Immunosuppressive medications such as azathioprine or methotrexate etc.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (3)

Novartis Investigative Site

Bursa, 16059, Turkey (Türkiye)

Location

Novartis Investigative Site

Kocaeli, 41380, Turkey (Türkiye)

Location

Novartis Investigative Site

Kütahya, 43000, Turkey (Türkiye)

Location

MeSH Terms

Conditions

Multiple Sclerosis; Nerve Degeneration

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

The trial was terminated due to low enrollment.

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 12, 2015
• First Posted: October 14, 2015
• Study Start: February 16, 2016
• Primary Completion: January 27, 2017
• Study Completion: January 27, 2017
• Last Updated: February 27, 2019
• Results First Posted: February 27, 2019

Record last verified: 2018-10

Data Sharing

• IPD Sharing: Will not share

Locations

TU (3)